The objective of this project is the elucidation of the molecular mechanisms invoved in the regulation of the proliferation and differentiation of adrenocortical cells and Leydig cells by the protein and polypeptide hormones of the pituitary gland. It is proposed to investigate the intracellular mechanisms that are altered in response to stimulatory and inhibitory extracellular signals. The fluctuations in intracellular concentrations of cyclic nucleotides and changes in the state of phosphorylation of nonhistone chromosomal proteins will be studied. The presence of an inducer of DNA synthesis in the S phase of proliferating cells will be examined. The changes in the adrenocortical cell surface as well as the cytoskeletal components induced by ACTH will be studied by surface labelling procedures and immunofluorescence techniques. The properties of the plasma membranes of normal and cancerous Leydig cells will be compared in order to elucidate the differences in the cell surfaces of normal and transformed cells. ACTH receptors will be characterized by binding studies with specifically tritiated hormone.